A PTEN variant uncouples longevity from impaired fitness in Caenorhabditis elegans with reduced insulin/IGF-1 signaling

Cited 13 time in webofscience Cited 0 time in scopus
  • Hit : 268
  • Download : 341
Insulin/IGF-1 signaling (IIS) regulates various physiological aspects in numerous species. In Caenorhabditis elegans, mutations in the daf-2/insulin/IGF-1 receptor dramatically increase lifespan and immunity, but generally impair motility, growth, and reproduction. Whether these pleiotropic effects can be dissociated at a specific step in insulin/IGF-1 signaling pathway remains unknown. Through performing a mutagenesis screen, we identified a missense mutation daf-18(yh1) that alters a cysteine to tyrosine in DAF-18/PTEN phosphatase, which maintained the long lifespan and enhanced immunity, while improving the reduced motility in adult daf-2 mutants. We showed that the daf-18(yh1) mutation decreased the lipid phosphatase activity of DAF-18/PTEN, while retaining a partial protein tyrosine phosphatase activity. We found that daf-18(yh1) maintained the partial activity of DAF-16/FOXO but restricted the detrimental upregulation of SKN-1/NRF2, contributing to beneficial physiological traits in daf-2 mutants. Our work provides important insights into how one evolutionarily conserved component, PTEN, can coordinate animal health and longevity. Mutations in daf-2/insulin/IGF-1 receptor impair the growth and reproduction of C. elegans but conversely enhance immunity and lifespan. Here, the authors show that a missense mutation in the gene retains the effects on lifespan and immunity and improves motility.
Publisher
NATURE PORTFOLIO
Issue Date
2021-09
Language
English
Article Type
Article
Citation

NATURE COMMUNICATIONS, v.12, no.1

ISSN
2041-1723
DOI
10.1038/s41467-021-25920-w
URI
http://hdl.handle.net/10203/288119
Appears in Collection
BS-Journal Papers(저널논문)
Files in This Item
121932.pdf(4.24 MB)Download
This item is cited by other documents in WoS
⊙ Detail Information in WoSⓡ Click to see webofscience_button
⊙ Cited 13 items in WoS Click to see citing articles in records_button

qr_code

  • mendeley

    citeulike


rss_1.0 rss_2.0 atom_1.0